Reaction products of halogens and alkoxylated primary amines

ABSTRACT

A DISINFECTANT COMPOSITION IS MADE BY REACTING A HALOGEN WITH AN AMINE OF THE FORMULA   R-N(-(CNH2N-O)P-H)-(CNH2N-O)Q-H   WHERE R IS A MONOVALENT HYDROCARBON RADICAL WITH UP TO 18 CARBON TOMS OR A HYDROXYALKYL RADICAL WITH FROM 2 TO 18 CARBON ATOMS, N IS 2, 3 OR 4 AND THE TOTAL OF P PLUS Q IS NOT LESS THAN 2 NOR MORE THAN 5. THE AMOUNT OF HALOGEN USED MAY BE 0.8 TO 1 ATOM EQUIVALENT PER MOLE EQUIVALENT OF AMINE AND AN EXCELLENT, STABLE, GERMICIDE AND FUNGICIDE IS PRODUCED. THE FUNGICIDAL QUALITIES MAY OFTEN BE ENHANCED BY INCREASING THE AMOUNT OF HALOGEN ABOVE THESE LIMIS, BUT THIS MAY BE AT THE EXPENSE OF THE STABILITY OF THE MATERIAL.

United States Patent 3,775,480 REACTION PRODUCTS 0F HALOGENS AND ALKOXYLATED PRIMARY AMINES Alan Geoflrey Scruton Glasby, Oxted, England, assignor to Glasby Pharmaceuticals Limited, Westerham, England No Drawing. Filed July 23, 1970, Ser. No. 57,795 Claims priority, application Great Britain, July 23, 1069,

37,033/ 69, 37,034/69, 37,035/69 Int. Cl. C07c 93/04 US. Cl. 260-584 B 7 Claims ABSTRACT OF THE DISCLOSURE A disinfectant composition is made by reacting a halogen with an amine of the formula n 2n )q where R is a monovalent hydrocarbon radical with up to 18 carbon atoms or a hydroxyalkyl radical with from 2 to 18 carbon atoms, 21 is 2, 3 or 4 and the total of p plus q is not less than 2 nor more than 5.

The amount of halogen used may be 0.8 to 1 atom equivalent per mole equivalent of amine and an excellent, stable, germicide and fungicide is produced. The fungicidal qualities may often be enhanced by increasing the amount of halogen above these limits, but this may be at the expense of the stability of the material.

This invention relates to disinfectant compositions.

Work has been done on the presentation of iodine by combination of this halogen with various materials including tertiary amines. Some of these materials are known as iodophors. The materials are substantially charge-transfer complexes and exhibit the characteristic ultraviolet spectrum and brown colour of such complexes. They are formed by the use of low temperature conditions during mixing.

This invention provides a new range of halogen-containing disinfectant materials, many of which are not charge-transfer complexes, as evidenced by the absence of charge-transfer bands in the ultraviolet spectrum.

The new materials can be made by the reaction of a halogen with an alkoxylated primary amine or mixture of such amines having the formula:

where R is a monovalent hydrocarbon radical with up to 18 carbon atoms or a hydroxyalkyl radical with from 2 to 18 carbon atoms; n is 2, 3 or 4 and the average of the totals of p plus q is not less than 1.5 nor more than 10, preferably'not less than 2 nor more than 5. Where R is a monovalent hydrocarbon it may be saturated or unsaturated, but is preferably the alkyl group C H where m is at least 3.

Mixtures of alkoxylated amines will usually be used because many amines from which they are made are available commercially as mixtures and the alkoxylation may not be uniform; indeed many amines sold as having predominantly a saturated alkyl chain often contain a small proportion of unsaturated material. However, a single alkoxylated amine may be used and then, of course, the average value of the total of p plus q will be an integer.

In preparing the materials very good results are achieved by the use of 0.8 to 1 atom equivalent of halogen (e.g. 0.4 to 0.5 mol equivalent of iodine taken as 1;) to each mole equivalent of amine. Within these proportions, it is possible, at any rate when R is one of the longer hydrocarbon chains, to make materials which show no charge-transfer bands in the ultraviolet spectrum. These materials are excellent bactericides and have fungicidal properties. If predominantly fungicidal qualities are required, it may be found desirable to add additional halogen, up to say 1.6 atom equivalents of halogen to each mole equivalent of amine, and this may well appear in the form of a charge-transfer complex.

The new materials may be made either in the absence of solvent, or in the presence of water or an organic solvent. It has been found desirable to make the materials of lower molecular weight in a solvent, as otherwise overheating may occur, with undesired side reactions. For a given R group, the solubility of the new materials increases with the number of alkoxy groups present. However the activity per unit weight decreases as the molecular weight increases.

The following non-limitative examples are given of disinfectants and their preparation in accordance with the invention.

EXAMPLE 1 29.9 lbs. (0.1 mol equivalent) of Ethomeen C/ 12 (the reaction product of 2 moles of ethylene oxide with cocoamine, commercially available from Armour Hess Chemicals Ltd.) were raised to a temperature of 50-55 C. and 12.7 lbs. of iodine were mixed into it. The temperature of the mixture rose to C. and after some 30 minutes, it was found that an aliquot of the mixture diluted to 1% w./v. with distilled water gave a pH in the range of 3.5 to 3.9 indicating completion of the reaction.

The product, which was a brownish-red, was soluble in water to give a disinfectant composition.

Its ultraviolet/visible and N.M.R. spectra are highly characteristic. The ultraviolet/visible spectrum as a 1% solution in methylene chloride, using a 1 cm. cell, gave the following peaks:

Wavelength, nm. Extinction coefiicient 285-295 8 345-360 3.5 505-510 (shoulder) 0.1 approx.

The N.M.R. spectrum using a tetramethyl silane standard gave the following results:

The disinfectant composition is germicidal in aqueous solution and kills both Gram-positive and Gram-negative bacteria; by way of example only tests show that Pseudomonas aeruquinosa, Staphylococcus aureus and Escherichia coli are destroyed. The material is also fungicidal and kills, for example, fungi of the genus Trichophyton, fungi of the genus Microsporum and Aspergillus fumigatus.

The material is notably resistant to organic contamination and in this respect it is as good as, for example, crude chloroxylenol whilst at the same time possessing markedly lower toxicity and irritancy. It is eifective in aqueous solution at a pH of less than 5 even in the presence of quite heavy contamination.

A typical formulation is an aqueous solution containing 4% of the complex and 2% of hydrogen chloride. This may be diluted one part in 40 parts of distilled water for heavy contamination and one part in 400 parts of distilled water for heavy contamination and one part in 400 parts of distilled water for light contamination.

If particularly required as a fungicide, the fungicidal properties of the material can be enhanced by formulating the material with up to 1.6 atom equivalents of iodine for every mol equivalent of the amine. This causes some of the iodine to become apparent as a charge-transfer complex, and the material becomes slightly more fungicidal at the expense of stability.

If too much iodine is added, the material is liable to become an insoluble oil.

EXAMPLE 2 If the same reaction is repeated using, in place of Ethomeen C/ 12 the equivalent weight of a commercial oleylamine of which each mol is condensed with 2-5 mols of ethylene oxide, a brownish opaque solid with disinfectant properties is produced.

EXAMPLE 3 150 grams of Ethomeen C/ 12 were heated to 90 C. and vigorously stirred. Chlorine gas was passed in and the temperature rose to 135 C. Further additions of chlorine gas was made at a rate which was controlled to maintain the temperature at 135 C. until 17.7 grams in all had been taken up. Stirring was continued for minutes and the mixture allowed to cool.

An aliquot diluted to 1% w./v. with distilled water gave a pH in the range of 3.5 to 3.9.

The product which had a brown colour had substantially the same powerful germicidal qualities and resistance to organic contamination as the product of Example 1.

EXAMPLE 4 145 grams (1 mol) of n-propyl diethanolamine are dissolved in 500 ml. methylene chloride, and 120 grams of iodine dissolved in 500 ml. methylene chloride are added slowly at room temperature.

The mixture may be left at room temperature for 24 hours when the material separates as an oil at the bottom of the vessel, whereupon the solvent can be decanted off.

Alternatively, the mixture of amine and iodine in methylene chloride can be brought to the boil immediately after mixing and the solvent boiled off; the rise in temperature occasioned by the boiling of the solvent causes the reaction between the amine and iodine to occur before the solvent is removed.

Lower members of the hydroxyalkyl series can be made similarly.

Although the materials of higher molecular weight can also be made similarly, getting rid of the solvent becomes more of a problem.

EXAMPLE 5 A molar solution of triethanolamine is reacted with a 0.5 molar solution of I (i.e. a one-atom equivalent) at a temperature of 40 to 50 C. The triethanolamine should be relatively pure, for example with a specification as follows:

Molecular weight 149.2 Specific gravity t/20 C. 1.128 Boiling point 760 mm. Hg, C. 286

Viscosity 20 C. (centistokes) 900 Both this material, and the similar product using tripropanolamine, are effective, easily prepared, disinfectants.

What is claimed is:

1. As a composition of matter the material obtained by reacting a halogen with at least one amine of the formula }CnH2no) H R-N CnHZnO) H where R is a monovalent alkyl or alkenyl radical with up to 18 carbon atoms or a hydroxyalkyl radical with from 2 to 18 carbon atoms, n is 2, 3 or 4 and the average of the totals of p plus q is not less than 1.5 nor more than 5.

2. The material of claim 1 where the average of the totals of p plus q is not less than 2 nor more than 5.

3. The material of claim 1 where R is the group C H where m is at least 3.

4. The material of claim 1 where the halogen is iodine or chlorine.

5. The material of claim 1 being the material obtained by reacting between 0.5 and 1 atom equivalent of the halogen with each mole equivalent of the amine.

6. The material of claim 5 where R is the group C H where m is at least 3.

7. The material of claim 5 where the halogen is iodine or chlorine.

References Cited UNITED STATES PATENTS 3,534,102 10/1970 Waldstein 260-584 B LEWIS GO'ITS, Primary Examiner R. L. RAYMOND, Assistant Examiner US. Cl. X.R. 424-325 

